Cagrilintide is a laboratory-made, long-acting counterpart of amylin — the hormone the pancreas secretes together with insulin after a meal, which tells the brain that you are full. It was developed by Novo Nordisk as a once-weekly obesity medicine, used alone or paired with semaglutide (the combination is called CagriSema). Unlike most “research peptides”, it has substantial human data behind it: a phase 2 trial with more than 700 participants and two phase 3 trials with several thousand people, published in the “New England Journal of Medicine” in 2025. The evidence for weight loss is therefore strong. At the same time, cagrilintide is not an approved medicine, and some popular claims about it — for instance that it “restores leptin sensitivity” — come from studies of other amylin analogues, not of cagrilintide itself. Below we set out what the publications actually show.
What cagrilintide is
Amylin is a peptide hormone released by the beta cells of the pancreas alongside insulin. It slows stomach emptying, suppresses glucagon release and — above all — signals satiety. As a medicine, however, it has two flaws: it circulates in the blood for only a very short time and it has a strong tendency to clump into amyloid fibrils (the same ones that build up in the pancreatic islets in type 2 diabetes). The first amylin analogue, pramlintide, is approved as an add-on to insulin in diabetes but needs three injections a day. Cagrilintide was designed to get around this: Kruse and colleagues (2021) describe it as a stable, “lipidated” amylin analogue — a molecule with a fatty-acid chain attached, thanks to which it works for a week. In a phase 1b trial the half-life of cagrilintide was 159–195 hours, roughly a week (Enebo et al., 2021).
How it works — amylin receptors in the brain
Amylin acts through an unusual “switch” (receptor): the calcitonin receptor joined to one of three helper proteins called RAMPs; depending on which protein is present, the result is an amylin receptor of type 1, 2 or 3. Cagrilintide activates both the amylin receptors and the calcitonin receptor itself — hence its description in the literature as a “dual amylin and calcitonin receptor agonist”. The key site of action is the area postrema — a part of the brainstem that lies outside the blood–brain barrier and “reads” hormones from the blood — together with neighbouring brainstem nuclei and the so-called parabrachial nucleus. In a study in obese mice (Carvas et al., 2025) cagrilintide lowered body weight (by 3.4 g in three weeks), but in mice lacking the RAMP1 and RAMP3 proteins, and therefore lacking amylin receptors 1 and 3, it lost potency, and activation of neurons in the area postrema was 57% lower. The authors conclude that the weight-lowering effect depends precisely on amylin receptors 1 and 3 in the brain. This is a different route from GLP-1 — which is why the two compounds are studied in combination.
Amylin and leptin — where that claim comes from
Descriptions of cagrilintide often say that it “restores leptin sensitivity”. It is worth knowing where this comes from. In 2008 a team from Amylin Pharmaceuticals (Roth et al.) showed in obese, leptin-resistant rats that pre-treatment with amylin partly restored leptin signalling in the hypothalamus, and that giving amylin and leptin together produced synergistic, “fat-specific” weight loss. The same paper described a 24-week study in humans with pramlintide plus recombinant leptin: 12.7% weight loss, more than with either drug alone. These are data on amylin and pramlintide, however, not on cagrilintide — leptin sensitivity has not been measured in the published human studies of cagrilintide. The claim is therefore plausible at the level of the drug class and of rodents, but for cagrilintide itself it remains untested.
Human data — cagrilintide alone
The most important study of cagrilintide on its own is the phase 2 trial published in the “Lancet” (Lau et al., 2021): 706 adults with overweight or obesity and without diabetes were randomised to five doses of cagrilintide (0.3–4.5 mg once weekly), to liraglutide 3 mg daily or to placebo for 26 weeks. Body weight fell by 6.0–10.8% depending on the dose, against 3.0% on placebo, and the highest dose (4.5 mg) was slightly more effective than liraglutide (10.8% vs 9.0%). The most common adverse events were gastrointestinal complaints (41–63% vs 32% on placebo, mainly nausea: 20–47% vs 18%) and injection-site reactions. In the phase 3 REDEFINE 1 trial (68 weeks) the cagrilintide-alone 2.4 mg arm had 302 participants; in the analysis assuming the treatment was taken, it produced 11.8% weight loss — against 16.1% for semaglutide 2.4 mg alone, 22.7% for the combination and 2.3% for placebo (figures quoted in the blood-pressure analysis of that trial, Verma et al., 2026). Cagrilintide alone therefore works, but less well than semaglutide. Its own phase 3 trials — including NCT07220642 (300 participants, 64 weeks) — are ongoing and have no results yet.
Human data — CagriSema, cagrilintide with semaglutide
The first data on the combination came from a phase 1b trial (Enebo et al., 2021): in 96 people the doses of both drugs were raised in parallel every four weeks over 16 weeks; after 20 weeks body weight had fallen by 15.7% (cagrilintide 1.2 mg) and 17.1% (2.4 mg), against 9.8% with semaglutide plus placebo. In a phase 2 trial of 92 people with type 2 diabetes (Frias et al., 2023, 32 weeks) CagriSema produced −15.6% body weight against −5.1% for semaglutide alone and −8.1% for cagrilintide alone, and glycated haemoglobin (HbA1c) fell by 2.2 percentage points. The decisive study was the phase 3 REDEFINE 1 trial (Garvey et al., 2025): 3,417 adults without diabetes, 68 weeks, CagriSema 2.4 mg/2.4 mg versus placebo. The mean change in body weight was −20.4% against −3.0% (a difference of 17.3 percentage points), and gastrointestinal adverse events were reported by 79.6% of people on CagriSema and 39.9% on placebo. The parallel REDEFINE 2 trial (Davies et al., 2025) enrolled 1,206 people with obesity and type 2 diabetes: −13.7% against −3.4% after 68 weeks, and an HbA1c of 6.5% or lower was reached by 73.5% of those treated against 15.9% on placebo. A secondary analysis of REDEFINE 1 (Verma et al., 2026) showed a fall in systolic blood pressure of 10.9 mm Hg against 2.8 mm Hg on placebo. The head-to-head comparison with tirzepatide — REDEFINE 4, NCT06131437, 809 participants, 84 weeks — was completed in December 2025 and has no peer-reviewed publication yet; according to the manufacturer's announcement of February 2026 the trial did not meet its primary objective, that is, it did not show CagriSema to be non-inferior to tirzepatide.
Safety and the limits of the evidence
Cagrilintide is not an approved medicine in any country; the US Drugs@FDA database lists no product containing it (as of September 2026). According to the manufacturer, an application for approval of CagriSema was submitted to the FDA in December 2025 and is awaiting a decision. All the large trials were funded by Novo Nordisk, and some of the authors are company employees. The side-effect profile is dominated by nausea, vomiting, diarrhoea and constipation — in REDEFINE 1 they affected four in five people treated, although they were usually transient and mild to moderate; with cagrilintide alone in phase 2, fewer than half of participants reported nausea. What is not known: how long the effect lasts after stopping, what the effect is on heart attacks and strokes (the REDEFINE 3 trial, NCT05669755, with 7,101 participants runs until 2027), and how the drug performs outside the trial populations. The efficacy data concern a pharmaceutical-grade medicine given under medical supervision with gradual dose escalation — they do not carry over to products from the unregulated market. We deliberately give no methods of use and no doses.
The wider context — a new axis alongside GLP-1
Cagrilintide is the most advanced amylin analogue in clinical development for obesity, but not the only one: further amylin and calcitonin receptor agonists are in phase 2 and 3 trials (Carvas et al., 2025). Its significance lies in acting through a different route from the incretin medicines — semaglutide or tirzepatide — which is why it can be combined with them, as the REDEFINE trials showed. The background to the whole group of metabolic medicines is covered in our piece on GLP-1, GIP and glucagon peptides.
Summary
Cagrilintide is a long-acting amylin analogue with a week-long duration of action that suppresses appetite through amylin receptors in the brainstem. On its own it lowers body weight by around 11% (phase 2 and a phase 3 arm), and combined with semaglutide by 20.4% over 68 weeks in people without diabetes and by 13.7% in people with type 2 diabetes — some of the strongest data in this whole encyclopaedia, because they come from large randomised phase 3 trials. The cost is frequent gastrointestinal complaints. The claim about “restoring leptin sensitivity” rests on studies of amylin and pramlintide in rats and on one small human study, not on studies of cagrilintide. The compound remains unapproved, and the application for CagriSema is awaiting assessment.
Sources
- Garvey WT, Blüher M, Osorto Contreras CK, et al.; REDEFINE 1 Study Group. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine. 2025;393(7):635–647. PMID: 40544433. DOI: 10.1056/NEJMoa2502081. pubmed.ncbi.nlm.nih.gov/40544433
- Davies MJ, Bajaj HS, Broholm C, et al.; REDEFINE 2 Study Group. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. The New England Journal of Medicine. 2025;393(7):648–659. PMID: 40544432. DOI: 10.1056/NEJMoa2502082. pubmed.ncbi.nlm.nih.gov/40544432
- Lau DCW, Erichsen L, Francisco AM, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet. 2021;398(10317):2160–2172. PMID: 34798060. DOI: 10.1016/S0140-6736(21)01751-7. pubmed.ncbi.nlm.nih.gov/34798060
- Frias JP, Deenadayalan S, Erichsen L, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023;402(10403):720–730. PMID: 37364590. DOI: 10.1016/S0140-6736(23)01163-7. pubmed.ncbi.nlm.nih.gov/37364590
- Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397(10286):1736–1748. PMID: 33894838. DOI: 10.1016/S0140-6736(21)00845-X. pubmed.ncbi.nlm.nih.gov/33894838
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- Carvas AO, Leuthardt A, Kulka P, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine. 2025;118:105836. PMID: 40609154. DOI: 10.1016/j.ebiom.2025.105836. pubmed.ncbi.nlm.nih.gov/40609154
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For in-vitro laboratory research only. It is not a human medicine and is not for treatment.